How Covid-19 attacks and kills certain brain cells

The interactions between Sars-CoV-2 and the brain have long been misunderstood and remain, even today, partly mysterious. For more than a year, researchers have been trying to determine how coronavirus enters the brain, whether it directly or indirectly causes neurological damage, or whether it is responsible for persistent symptoms such as disturbances in attention and speech, concentration, and even other mental illnesses. Researchers have already discovered that Sars-CoV-2 is responsible for a panel of neuroradiological attacks, including strokes, microbleeds of the brain, inflammation of the meninges, and attacks of white or gray matter; and it can also cause neurological disorders such as loss of taste, smell, and even some rare eye complications. But the mechanisms by which Sars-CoV-2 causes these attacks are not yet all identified.

Until now, the scientific consensus was that most were not caused by the coronavirus itself, but by inflammation caused in reaction to the disease. A new study published this Thursday in Nature Neuroscience by an international team that brings together researchers from Inserm, the Institut Pasteur de Lille and the CNRS, shows for the first time that Sars-CoV-2 is capable of directly attacking the blood vessels of the brain. The cerebral vascular endothelial cells, essential components of the blood-brain barrier (BBB) ​​that protect the brain, are affected by a phenomenon of cell death, they explain. “This awareness of the severity of SARS-CoV2 infection and its consequences for the proper functioning of our brain is essential to allow the best possible management of patients who have been infected in the coming years,” explains Vincent Prévot, research director. de Inserm and a co-author of the study, in a press release.

The defense barrier against attacked foreign substances.

Endothelial cells line all blood vessels in the human body and play a vital role in the development and maintenance of vascular functions. Endothelial cells in the brain are also components of the BBB, whose main function is to isolate the central nervous system from the bloodstream. This barrier, which acts as a filter, prevents foreign substances or potentially toxic molecules from entering the brain and spinal cord while allowing the transfer of essential nutrients for their activity. Therefore, the vascular endothelial cells of the brain play an essential role in the proper blood supply to the brain and its proper functioning. However, after having analyzed the brains of patients killed by SARS-CoV-2, the researchers discovered that the infection can lead to the death of endothelial cells in the brain. This attack causes the appearance of “ghost vessels” in the brain, which are empty blood vessels devoid of endothelial cells, which affects the effectiveness of the BBB.

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Using state-of-the-art techniques such as transgenesis, single-cell RNA sequencing, mass spectrometry, and super-resolution microscopy, the research team was able to determine how this attack plays out. According to them, Sars-CoV-2 is capable of “hacking” endothelial cells to make them molecular scissors. These will then cut the proteins called Nemo, which are essential for endothelial cell survival.

Long-term consequences?

The death of vascular endothelial cells in the brain can have two important consequences, the researchers note. On the one hand, a temporary breakdown of the blood-brain barrier, which causes microbleeds in areas where the blood is not supposed to access freely. On the other hand, hypoperfusion – a decrease in blood flow – to certain regions of the brain, which could lead to the death of the patient in the most severe cases. Fortunately, these effects would not be irreversible in less severe cases, the researchers say.

However, one question remains: even if it is temporary, can the phase during which the brain is less supplied with water have longer-term consequences? The hypothesis remains to be verified, say the study authors, who believe that this phenomenon could predispose some people who have contracted the disease to develop cognitive, neurodegenerative disorders or even dementia. This discovery, while worrying, should allow better care for Covid-19 victims who would show such signs in the future.

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According to the results of a large American study published in The Lancet Psychiatry, 13% of patients were diagnosed with neurological or psychiatric disorders for the first time in their lives within six months of infection. Anxiety (17%) and mood disorders (14%) are the most frequent, but also those related to the use of psychoactive substances (7%) or insomnia (5%). The incidence of neurological disorders such as stroke, brain bleeds, and dementia, on the other hand, are much rarer, but increase if former patients have developed a particularly severe form of Covid-19.

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